The determination of cardiac output, or measurement of the blood volumetric output of the heart is of substantial importance for a variety of medical situations. Intensivists utilize such information along with a number of additional pulmonary factors to evaluate heart patients within intensive care units. A variety of approaches have been developed for measuring this output, all of which exhibit certain limitations and/or inaccuracies. In effect, the volumetric aspect of cardiac output provides information as to the sufficiency of oxygen delivery to the tissue or the oxygenation of such tissue. When combined with other measurements, an important evaluation of the status of the cardiovascular system of a patient may be achieved.
Currently, the more accepted approach for deriving cardiac output values is an indicator dilution technique which takes advantage of refinements made earlier in pulmonary catheter technology. With the indicator dilution approach, a signal is inserted into the blood upstream from the pulmonary artery, and the extent of signal dilution can then be correlated with stroke volume or volumetric output of the heart. Of these indicator dilution methods, thermodilution is the present technique of choice, and in particular, that technique employing a cold liquid injectate as the signal. This approach is invasive, requiring placement of a Swan-Ganz pulmonary artery catheter such that its tip or distal end functions to position a temperature sensor just beyond the right ventricle within the pulmonary artery. The indicator employed is a bolus of cold isotonic saline which is injected from the indwelling catheter into or near the right atrium. Downstream blood temperature then is monitored to obtain a dilution curve relating temperature deviation to time, such curves sometimes being referred to as "wash out" curves. Combining the area under this thermodilution curve with the amount of energy subtracted by cooling of the blood provides a measure of the rate at which the heart is pumping blood, such rate usually being expressed in liters per minute. If cardiac output is high, the area under the thermodilution curve for a given applied energy, Q, will be relatively small in accordance with the well-known Stewart-Hamilton relationship. Conversely, if cardiac output is low, the area under the thermodilution curve for a given amount of applied energy, Q, will be relatively large. See in this regard:
Ganz, et al., "A New Technique for the Measurement of Cardiac Output by Thermodilution in Man," American Journal of Cardiology, Vol. 27, April, 1971, pp 392-396. PA1 Afonzo, S., et al., "Intravascular and Intracardiac Blood Temperatures in Man," Journal of Applied Physiology, Vol. 17, pp 706-708, 1962. See also, U.S. Pat. No. 4,595,015. PA1 "Instantaneous and Continuous Cardiac Output Obtained with a Doppler Pulmonary Artery Catheter," Journal of the American College of Cardiology, Vol. 13, No. 6, May, 1989, pp 1382-1392. PA1 "Transtracheal Doppler: A New Procedure for Continuous Cardiac Output Measurement," Anesthesiology, Vol. 70, No. 1, January 1989, pp 134-138. PA1 "Continuous Cardiac Output Monitoring During Cardiac Surgery," Update in Intensive Care and Emergency Medicine, Berlin: Springer-Verlag, 1990, pp 413-417. PA1 "Alternatives to Swan-Ganz Cardiac Output Monitoring" by Moore, et al., Surgical Clinics of North America, Vol. 71, No. 4, August 1991, pp 699-721. PA1 (a) providing a catheter having a proximal end region extending to a measurement region, an indicator channel within the catheter having a fluid input at the proximal end region and extending to an infusion outlet at the measurement region from which analyte-containing fluid may be expressed, an analyte concentration sensor mounted with the catheter having a forward assembly contactable with flowing blood at the measurement region at a location spaced from the infusion outlet a dilution measurement distance, the sensor being responsive to the concentration of an analyte to provide an output corresponding with the concentration of analyte in blood, and having a capability for providing the output within an infusion interval achieving a cardiac output measurement frequency interval of about one to three minutes; PA1 (b) positioning the catheter within the bloodstream of the body locating the measurement region at the heart region of the patient in a cardiac output orientation wherein the analyte concentration sensor is downstream within the bloodstream from the infusion outlet; PA1 (c) providing a source of analyte-containing fluid biocompatible with and metabolizable within the body such analyte being independent of the thermal energy content of the fluid and having a predetermined indicator concentration; PA1 (d) deriving a baseline value corresponding with the concentration of analyte in the bloodstream from the concentration sensor output; PA1 (e) delivering the analyte-containing fluid from the source into the indicator channel input at a predetermined mass flow rate for an infusion interval; PA1 (f) deriving a subsequent value corresponding with the concentration of analyte in the bloodstream from the concentration sensor output during the infusion interval; and PA1 (g) deriving the value for the cardiac output of the heart of the body by correlating the baseline value, the subsequent value, the predetermined indicator concentration, and the predetermined mass flow rate.
In a typical procedure, a cold bolus of saline at ice or room temperature in an amount of about 5-10 milliliters is injected through the catheter as a measurement procedure which will require about two minutes to complete. For purposes of gaining accuracy, this procedure is repeated three or four times and readings are averaged. Consequently, the procedure requires an elapsed time of 4-5 minutes. In general, the first measurement undertaken is discarded inasmuch as the catheter will have resided in the bloodstream of the body at a temperature of about 37.degree. C. Accordingly, the first measurement procedure typically is employed for the purpose of cooling the dilution channel of the catheter, and the remaining measurements then are averaged to obtain a single cardiac output value. Thus, up to about 40 ml of fluid is injected into the pulmonary system of the patient with each measurement which is undertaken. As a consequence, this procedure is carried out typically only one to two times per hour over a period of 24 to 72 hours. While practitioners would prefer that the information be developed with much greater frequency, the procedure, while considered to be quite accurate, will add too much fluid to the cardiovascular system if carried out too often. Of course, the accuracy of the procedure is dependent upon an accurate knowledge of the temperature, volume, and rate of injection of the liquid bolus. Liquid volume measurements during manual infusions are difficult to make with substantial accuracy. For example, a syringe may be used for injecting through the catheter with the result that the volume may be identified only within several percent of its actual volume. Operator error associated with volume measurement and rate of injection also may be a problem. Because the pulmonary catheters employed are somewhat lengthy (approximately 30 to 40 inches), it is difficult to know precisely the temperature of the liquid injectate at the point at which it enters the bloodstream near the distal end of that catheter. Heat exchange of the liquid dispensing device such as a syringe with the catheter, and the blood and tissue surrounding the catheter upstream of the point at which the liquid is actually released into the blood may mean that the injectate temperature is known only to within about five percent of its actual temperature. Notwithstanding the slowness of measurement and labor intensity of the cold bolus technique, it is often referred to as the "gold standard" for cardiac output measurement by practitioners. In this regard, other techniques of determining cardiac output typically are evaluated by comparison with the cold bolus approach in order to determine their acceptability.
Another technique of thermodilution to measure cardiac output employs a pulse of temperature elevation as the indicator signal. In general, a heating coil is mounted upon the indwelling catheter so as to be located near the entrance of the heart. That coil is heated for an interval of about three seconds which, in turn, functions to heat the blood passing adjacent to it. As is apparent, the amount of heat which can be generated from a heater element is limited to avoid a thermocoagulation of the blood or damage to tissue in adjacency with the heater. This limits the extent of the signal which will be developed in the presence of what may be considered thermal noise within the human body. In this regard, measurement error will be a result of such noise phenomena because of the physiological blood temperature variation present in the body. Such variations are caused by respirations, coughing, and the effects of certain of the organs of the body itself. See in this regard:
This thermal noise-based difficulty is not encountered in the cold bolus technique described above, inasmuch as the caloric content of a cold bolus measurement is on the order of about 300 calories. By contrast, because of the limitations on the amount of heat which is generated for the temperature approach, only 15 or 20 calories are available for the measurement. Investigators have attempted to correct for the thermal noise problem through the utilization of filtering techniques, for example, utilizing moving averages over 6 to 12 readings. However, where such corrective filtering approaches are utilized, a sudden downturn in the hemodynamic system of a patient will not be observed by the practitioner until it may be too late. The effective measurement frequency or interval for this technique is somewhat extended, for example about 10 minutes, because of the inaccuracies encountered. In this regard, a cardiac output value is achieved only as a consequence of a sequence of numerous measurements. In general, the approach does not achieve the accuracy of the above-discussed cold bolus technique. Thermodilution techniques involving the use of electrical resistance heaters are described, for example, in U.S. Pat. Nos. 3,359,974; 4,217,910; 4,240,441; and 5,435,308.
Other approaches to the elimination of an injectant in thermodilution procedures have been, for example, to introduce the thermal signal into the flowing blood by circulating a liquid within the catheter, such liquid preferably being cooler than the blood temperature. See in this regard, U.S. Pat. No. 4,819,655. While, advantageously, no injectant is utilized with such procedure, the method has the disadvantage that only a limited thermal signal is available as compared with the cold bolus approach, and, thus, the measurement is susceptible to error due to physiological temperature variations. As another example, a technique has been proposed wherein a stochastic excitation signal present as a series of thermal pulses of varying duration is asserted within the bloodstream, and the resultant output signal downstream, now present as blood temperature variation, is measured. The blood flow rate then is extracted by cross-correlating the excitation signal and measured output signal. See U.S. Pat. No. 4,507,974.
Dilution and conductivity dilution techniques, also involving injection of an auxiliary liquid such as a dye or saline solution into the bloodstream are known. See in this regard, U.S. Pat. Nos. 3,269,386; 3,304,413; 3,433,935; 3,820,530; 4,572,206; and 5,092,339. A resulting dilution or conductivity dilution curve will be seen to be similar to the above-discussed thermodilution curve. Dilution and conductivity dilution procedures exhibit certain of the deficiencies discussed in connection with the injected liquid bolus-based thermodilution approach, namely difficulty in precisely controlling the rate of manual injection and measuring the injectate volume as well as an unsuitability of the procedure for frequent or repeated use over long periods of time. The above-noted dye dilution procedures have been employed for a relatively extensive period of time. In general, a dye is injected into the bloodstream and then a blood sample is drawn, typically from a major artery, at various intervals of time. The technique is quite labor intensive and, because of the extensive amount of dye which is required to obtain an accurate measurement. The frequency of measurement is very low. In particular, if the frequency is attempted to be enhanced, then the signal-to-noise ratio encountered becomes unacceptable as the background color of the blood continues to change. The saline solution approach involves the injection of a hypertonic saline solution having a much higher salt content per unit volume than, for example, typical isotonic saline solution which is about 0.9% sodium chloride. Following injection of the hypertonic saline solution, the electrical resistivity of the blood is evaluated. The method has been criticized inasmuch as such an extensive amount of electrolyte is added to the blood for each measurement, the electrolyte balance in the body becomes adversely affected. Note that the technique looks at electrical charges in a direct fashion as they exist in the bloodstream. Another indicator-dilution method for determining cardiac output involves the utilization of a cation, preferably lithium, which is not already present in the blood. This cation is injected as a bolus into the blood. A cation selective electrode is used to measure concentration and subsequently develop a resulting cation dilution curve in a manner similar to a thermodilution measurement. Cation-dilution cardiac output measurement methods share certain of the same deficiencies as discussed above for liquid-bolus-based thermodilution methods. See U.S. Pat. No. 5,395,505.
Ultrasonic echocardiography has been employed for the instant purpose. With this invasive method, a plurality of microbubbles is introduced into the blood upstream of the measurement position. As described in U.S. Pat. No. 4,316,391, an ultrasonic pulse is generated from a position opposite and spaced from the region of the flowing microbubbles, for example, using an ultrasonic transducer/receiver located outside of the body. A reflective ultrasonic image, created by reflection of the ultrasonic pulse from the microbubble dispersions is measured and correlated with cardiac output, i.e. flow rate, using conventional dilution techniques. This method preferably employs microbubbles comprising a gelatin membrane-encased "inert" gas such as nitrogen or carbon dioxide to perform each measurement. As a consequence, the method is not suitable for performing clinical measurements continuously or even intermittently for an extended period of time due to the accumulation of bubble membrane material that must be cleared from the body by the body's own cleansing processes.
A derivation of cardiac output by simultaneously measuring blood velocity and vessel geometry has been described, for example, in U.S. Pat. Nos. 4,733,669 and 4,869,263. With this approach, a Doppler pulmonary artery catheter system is provided which develops instantaneous vessel diameter measurements and a mapping of instantaneous blood velocity profiles within the main pulmonary artery. From such data, an instantaneous cardiac output then is calculated. See in this regard the following publication:
A similar approach has been described which involves a technique wherein a piezoelectric ultrasound transducer is placed in the trachea of a patient in proximity to the aorta or pulmonary artery. Ultrasound waves then are transmitted toward the path of flow of blood in the artery and are reflected and received. The cross-sectional size if the artery is measured, based upon the Doppler frequency difference between the transmitted and received waves. Imaging techniques such as X-ray or radioisotopic methods also have been used. See generally the following publication:
See additionally, U.S. Pat. Nos. 4,671,295 and 4,722,347.
A pulse contour technique for measuring blood velocity which requires a secondary calibration is described in the following publication:
Another approach employs a so-called "hot wire" anemometer or heated thermistor as described in U.S. Pat. No. 4,841,981; EP 235811; U.S. Pat. No. 4,685,470, and WO88/06426.
Any of the velocity-based measurement techniques for deriving cardiac output confront a rather basic difficulty not present with indicator dilution approaches. That difficulty resides in the necessity for knowing the geometric cross section of the vessel through which blood is flowing. In this regard, the geometry and diametric extent of the pulmonary artery is not known and is dynamic, changing with the pulsation nature of blood flow. Of course, the velocity measurements themselves must account for the surface effect of the interior of the vessel, velocity varying from essentially a zero value at the interior surface or lumen of the vessel to a maximum value towards the interior of that vessel.
A non-invasive technique evaluating thorasic electrical bioimpedance to derive cardiac outputs has been studied, for example, using electrocardiographic signals (ECG). However, cross-correlation of the results with the well-accepted thermodilution technique have led to questions of reliability.
For a general discourse looking to alternatives to the current indicator dilution method of choice, reference is made to the following publication:
What is called for in this hemodynamic field of endeavor is an approach to cardiac output measurement which permits the generation of a cardiac output value of accuracy at least commensurate with the cold bolus technique at a measurement frequency much higher than currently available, for example, at intervals of 1 to 3 minutes. The technique employed must not be labor intensive in view of the current cost constraints encountered by clinicians. Of corresponding importance, the technique cannot adversely alter the body stability of the patient, i.e., the blood component should not be adversely diluted or changed to the extent that the treatment evokes iatrogenesis.